Adding Azathioprine to Tacrolimus Slows Fibrosis Onset in Liver Transplant Recipients With HCV, Cirrhosis

Presented at EASL

By Shazia Qureshi

AMSTERDAM, the Netherlands -- April 27, 2013 -- Adding azathioprine to tacrolimus led to a slower onset of severe fibrosis in patients who received a liver transplant because of hepatitis C virus (HCV)-related cirrhosis, according to a study presented at the 48th Annual Meeting of the European Association for the Study of the Liver (EASL).

In addition, the combination therapy seemed to lower the chance of portal hypertension.

The findings of the 8-year study were presented on April 25 by Pinelopi Manousou, MD, Royal Free Sheila Sherlock Liver Centre, at the University College London, London, United Kingdom.

“Optimal immunosuppression treatment for these patients is still under debate” she said. “Immunosuppression worsens the severity of HCV recurrence.”

A total of 103 adult patients were randomised to receive either tacrolimus monotherapy (n = 54) or triple therapy (n = 49), which consisted of tacrolimus (0.1 mg/kg in divided doses), azathioprine (1 mg/kg), and prednisolone (20 mg/day, then tapered off to zero by 3 to 6 months).

Time to stage 4 fibrosis (on the Ishak scale of 0 = no fibrosis to 6 = cirrhosis) was one of the primary endpoints.

Over a median of 96 months of follow-up, stage 4 fibrosis was reached by 19 patients on monotherapy and by 11 patients taking triple therapy, with the triple therapy group showing slower fibrosis progression (median of 49 months vs 32 months with monotherapy; P = .005).

The researchers also measured fibrosis using the collagen proportionate area (CPA). Among those patients in whom it was measured, CPA was found to be ≥6% in 20 of 39 patients in the monotherapy group and in 13 of 39 patients in the triple therapy group. When the cut-off used was ≥7.2%, this was seen in 21 of 39 patients in the monotherapy group and in 14 of 39 patients in the triple therapy arm.

Portal hypertension was defined as hepatic venous pressure gradient (HVPG) ≥10 mmHg. Among those in whom HVPG was measured, it was found to be ≥10 mmHg in 11 of 33 patients in the monotherapy group and in 4 of 31 patients in the triple therapy group.

“The triple therapy arm has the lowest fibrosis progression rate published in the literature to date,” said Dr. Manousou. “This regimen could be considered as a first choice for HCV [liver] transplant patients, until such time as other evidence proves otherwise.”

[Presentation title: Long Term - 8 Year Follow-Up of a Randomized Trial of Tacrolimus Monotherapy versus Triple Therapy After Liver Transplantation for HCV Cirrhosis. Abstract 25]

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